Potassium channel openers such as minoxidil (Upjohn), pinacidil (Lilly) and diazoxide (Shiseido and Schering-Plough) are known for their hair growth stimulating activity. Thus, U.S. Pat. Nos. 4,596,812 and 4,139,619 disclose use of minoxidil in the treatment of male pattern baldness, alopecia areata and balding in females. U.S. Pat. No. 4,057,636 discloses pinacidil. DE 3,827,467A discloses combinations of minoxidil and hydrocortisone or retinoids.
U.S. Pat. No. 5,011,837 to Atwal et al discloses aryl cyanoguanidines which possess potassium channel activating activity and are useful therapy for hypertension and other cardiovascular disorders, for various central nervous system disorders, kidney and urinary problems as well as for the promotion of hair growth, for example in the treatment of male pattern baldness (alopecia). These aryl cyanoguanidines have the structure ##STR1##
and its possible tautomers ##STR2##
and ##STR3##
including pharmaceutically acceptable salts, wherein
R.sub.1 is alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, aryl, arylalkyl or cycloalkylalkyl;
R.sub.2 is ##STR4##
R.sub.3 and R.sub.4 are each independently selected form --R.sub.2, hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, halo, alkoxy, --NHalkyl, --N--(alkyl).sub.2, --S-alkyl, --O-aryl-alkyl, --S--arylalkyl or --S-aryl, --O-aryl, --NHaryl-alkyl, or R.sub.2 and R.sub.3 taken together are a group which form a ring with the two carbon atoms to which they are attached, which group is selected from ##STR5##
wherein
m=1 or 2,
n=3-5,
p=2-4,
X is 0, NR.sub.5, CH.sub.2 ; and
R.sub.5 is hydrogen or R.sub.1.
Example 1 of U.S. Pat. No. 5,011,837 discloses the preparation of 4-[[(cyanoimino)-[(1,2,2-trimethylpropyl)amino]benzonitrile ##STR6##
in the form of its racemic mixture.
PCT Application WO 92/02225 discloses a combination of a potassium channel opener and a 5-.alpha.-reductase inhibitor for promoting hair growth.
PCT Application WO 92/09259A discloses use of an androgen blocker and a potassium channel activator for stimulation of hair growth.